Early treatment is key, but huge disparities still remain

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A
study from the US has found that some groups of people with HIV, especially
those treated before their CD4 count falls below 350 cells/mm3, now
have life expectancies equal to or even higher than the US general population.

However,
it also finds that life expectancy for some other groups – most notably women
and non-white people – is still considerably below comparable members of the general
population and that for people who inject drugs, life expectancy in the era of
antiretroviral therapy (ART) has not improved at all.

A
second study, which looked at death rates among both HIV-positive and HIV-negative members of two cohorts of people with or at risk of HIV, has found
that the death rate from non-AIDS-defining illnesses among people with HIV who
started ART above the 350 cells/mm3 threshold was not, and never has
been, any higher than among comparable HIV-negative people.

In other words, the
sole contributor to the increased mortality in people who started ART early was AIDS. This was not, however, the case
for people who started ART later, who had raised mortality due to
non-AIDS-related causes as well as due to AIDS.

Life expectancy in people on therapy, 2000-2007

The
first study looked at death rates among, and then computed life expectancy for,
22,937 people with HIV in the US and Canada who started ART between the
beginning of 2000 and the end of 2007. It compared their life expectancy at age 20 with the general population
and noted how it had changed in the study’s eight years.

Life
expectancy at age 20 in the US population is approximately 57 years in men
(i.e. on average, and in the absence of further change, 50% will die by
the age of 77) and 62 years in women (i.e. 50% chance of death by 82). In Canada,
men can expect to live nearly three years longer than this and women just over
two.

The
study found that for the group as a whole and over the full eight years, the
average life expectancy in people with HIV was just under 43 years, i.e. 50% will die by the age of 63 – 15 years earlier than men and 19 years earlier than women in the general US population.

However,
there were huge disparities in life expectancies between different groups.
Whereas people who inject drugs only had a life expectancy of 29 more
years at age 20, for white people it was 52 years, for those starting treatment with a
CD4 count above 350 cells/mm3 it was 55 years and for gay men it was
57 years – the same (or slightly higher) than in US men in general.

Furthermore,
life expectancy had improved dramatically between 2000 and 2008 for most
groups. In non-white people, even though life expectancy for those on ART
between 2005 and 2007 was still only 48 more years at age 20 – i.e. nine years behind US men and 14 years behind
US women – this was a dramatic improvement since 2000-2002 when non-white people on
ART could expect, on average, to die at 50 – a gain of 18 years.

Life
expectancy at age 20 had gone up 17 years in men, 10 years in women (though
notably, this had not improved since 2005), by 13 years in gay men, by 12.5
years in heterosexual people, and by 20 years in those starting ART at
CD4 counts over 350 cells/mm3.

This
means that average life expectancy at age 20 was now equal to US men in the general population, among
heterosexual people with HIV and in white people. It was also a remarkable 69 years
at age 20 in gay men and people starting ART before 350 cells/mm3 –
meaning that, if nothing else changed, these groups, as long as they stay on
ART, have a 50/50 chance of seeing their 89th birthday – a full seven years
longer than women in the general US population.

In
contrast, life expectancy at age 20 in people who inject drugs had not changed at
all and was still 29 years at age 20 in 2007, as it was in 2000.

Another
sobering finding was that only 28% of the cohort had started ART before their
CD4 count fell below 350 cells/mm3, though this proportion had
improved over time.

Mortality rates in HIV-positive and -negative people

One
of the problems with this kind of study is that like is not being compared with
like. People with HIV will have many differences other than their status and
their medication from the average member of the public, so differences in
mortality could be due to all sorts of other factors.

A
second study of mortality tried to get around this by comparing death rates in
people who, apart from their HIV status, were closely similar. By doing this, it
was able to tease out the proportion of deaths that were due to AIDS and
therefore whether deaths due to non-AIDS-defining illness were any higher in
people with HIV or on ART than they are in the general population.

This
study looked at mortality due to AIDS-defining and non-AIDS defining illness in
two long-standing US cohort studies – the Multicenter AIDS Cohort Study
(MACS)
and the Women’s
Interagency HIV Study (WIHS). These long-standing cohort
studies were set up in 1985 and 1993 respectively. MACS has recruited 6972 gay
men who are either HIV positive or at high risk of HIV infection (41% with HIV
at enrolment) and WIHS has recruited 4137 women who are either HIV positive or closely
matched to the HIV-positive women in terms of characteristics (38% with HIV at
enrolment).

This
study compared mortality rates between the HIV-negative cohort members and the
ones with HIV who were on combination antiretroviral therapy (cART). Because
there were not large numbers of cohort members on cART who were either young or
very old, it only looked at mortality in the ‘middle years’, between 35 and 70.
For the people with HIV it looked only at mortality subsequent to them starting
cART if they were older than 35 when they started. The study looked at
mortality up to the end of 2010, so some people could have been on cART of
various kinds for 15 years or more, if they started in the mid-1990s and were
aged 35 to 55 at the time. Average length of follow-up was in fact 10.2 years:
11.7 years in the HIV-negative people and 7.6 and 8.1 years (depending on CD4
count at cART initiation) in the HIV-positive people on cART.

A
high proportion of the cohorts – 60% or 6699 individuals – were included in
this study. The first and most obvious fact is that mortality was a lot higher
in the people with HIV, as you might expect: over the years, 540 out of 2953
people with HIV died (18.2%) compared with 165 out of 3854 HIV-negative people
(3.4%). In terms of annual mortality rates, this is 2.32% per year in the people
with HIV and 0.37% per year in the HIV-negative people.

The
researchers then divided deaths in the people with HIV into AIDS-related and
non-AIDS-related causes: 11.5% of the people with HIV died of AIDS and 6.7% of
other conditions.

In
one specific group, namely people with HIV who started cART with a CD4 count
over 350 cells/mm3, mortality due to non-AIDS illness was no higher
than it was in the HIV-negative people. However, even in this group, AIDS deaths
predominated, more than doubling mortality, so overall mortality in this group
was approximately 1% per year compared with approximately 0.4% in the HIV-negative
people. This probably reflects the fact that many people would have died in the
early years of sub-standard cART.

This
is reflected in the fact that if people died of AIDS-related illness, they
tended to do so much younger. Models were done that, based on the mortality
rates seen, projected the likely future mortality rates of people over 70.
These showed that in people who started cART at a CD4 count above 350 cells/mm3
and who died of AIDS, there was a 50% chance of death by the age of 54: in
those who died of non-AIDS-related illness, 50% was not reached till the age of
75, no different from HIV-negative people. Thus people starting ART early were
living near-normal lifespans as long as they avoided early death from AIDS,
probably reflecting the generally improved lifespan and vastly decreased AIDS
incidence of those who survived beyond the early 2000s.

The
non-AIDS-related mortality in people who started cART at lower CD4 counts,
however, was higher than in HIV-negative people. It was 66% higher in people
starting cART at CD4 counts between 200 and 350 cells/mm3 and 115%
higher in people starting it at CD4 counts below 200 cells/mm3,
reinforcing the message that starting ART early is generally better for the
health, not only because it stops AIDS-related illness. Other factors that
increased the chance of death for people on cART were smoking (50% higher AIDS mortality
and 120% higher non-AIDS mortality in smokers); depression (65% more non-AIDS
mortality and 58% more AIDS mortality); and high blood pressure (42% higher
AIDS and 30% higher non-AIDS mortality).

The
women in WIHS had 40% higher mortality due to non-AIDS illness than the men in
MACS, but no higher AIDS mortality.

The
biggest influence on non-AIDS mortality was hepatitis B or C co-infection. This
more than doubled non-AIDS mortality. HIV-negative people with hepatitis B or C
died on average eight years younger than those without, and people with co-infection on cART 15 years younger than those with HIV alone.

More comparative data needed

In
a separate editorial on the second paper, researchers Veronica Miller and Sally
Hodder commented that improvements in life expectancy might be expected to
continue in MACS and WIHS. They added that the second paper adds considerably
to the evidence for earlier initiation of antiretroviral therapy; noting that over
40% of non-AIDS and non-hepatitis deaths were due to cardiovascular disease, and
that non-AIDS deaths were higher in people who started ART later. They add that
the paper continues to beg the question of whether inflammatory processes in untreated
people with HIV do add to the risk of cardiovascular disease at lower CD4 counts.

Pointing
out that the robustness of the findings on life expectancy and cause of death in
the study is due to the accumulation of 25 or more years of data, they make a
plea for continued government support of large cohort studies, saying: “Continued
public funding of cohorts such as MACS, WIHS and others will be even more
important as we enter the fourth decade of antiretroviral treatment and seek to
optimise strategies to improve individual and public health.”

References

Samji H et al. Closing the gap: increases in life
expectancy among treated HIV-positive individuals in the United States and
Canada. PLOS ONE 8(12): e81355. Doi:10.1371/journal.pone.0081355. 2014.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.